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Culver lab develops nationally impactful meth inhibiting drug

It's a story that's been picked up by national media outlets like BusinessWeek and Forbes, about a product with the potential to make a real impact in a drug abuse epidemic which has especially plagued rural America -- including the Marshall County area -- in recent years. And it was developed in Culver, Indiana.

Many here drive by the Acura Pharmaceuticals plant regularly -- even daily -- without paying the nondescript property much heed. Many more may not be aware it no longer operates under the Houba moniker (see article this issue).

Acura's corporate office is actually in Palatine, Ill., and president and CEO Bob Jones works out of an office in his New Jersey home, though he notes "all of the technical work" on the company's new drug, Nexafed, “was the work of the people in the Culver facility. It was not born someplace else and they were peripherally involved. It took place within the four walls in Culver, the work of our scientists and folks there."

That work is the development of an alternative to currently popular over-the-counter medications rampantly abused in the manufacture of illegal methamphetamine, or "meth," as most readers are all too well aware. Specifically, Nexafed is a pseudoephedrine hydrochloride (HCl) non-prescription medication which utilizes what scientists at Acura have dubbed Impede, a combination of safe and inactive ingredients which disrupt the conversion of pseudoephedrine into meth.

What this means, specifically, says Ron Leech, Senior Director of Quality and Analytical Chemistry at the Culver Acura plant, is that consumers can expect Nexafed to offer the same relief of cold or allergy symptoms they're used to from pseudoephedrine medications like Sudafed while being less attractive to those wishing to make meth.
Statistics concerning abuse of methamphetamine are staggering, though unlikely to shock those familiar with the headlines. In 2011, 439,000 Americans age 12 and older have abused methamphetamine at least once in the past year, and more than 10,000 underground labs were found in the U.S., creating a huge array of environmental hazards. In 2005, methamphetamine use cost U.S. taxpayers an estimated $23.4 billion, including related health care, incarceration and parole supervision, lab cleanups, property damage, drug arrests, hospital costs, custodial care for children, lost productivity, lower quality of life and premature death. Meth, of course, is highly addictive and highly destructive to the addict's health.

Marshall County residents know the numbers hit home hard. This county was ranked 9th in the state of Indiana by the State Police in number of meth labs in 2011 (nearby Kosciusko County was 3rd and Elkhart 2nd); Marshall was 8th in the state in 2010. Lest Culver readers think themselves immune, there have been a handful of meth-related arrests within town limits in the past year as well.

"This is a huge problem," says Jones, "and not just in Indiana; it's a national problem."

One unfortunate side effect of the war on meth, Jones points out, is that sometimes its "pitting law enforcement against legitimate consumers. Law enforcement wants to solve their problem and consumers want to treat allergies and colds. It has become somewhat of a battle -- we have new laws which put Pseudoephedrine products behind the counter, limiting access to what is a very effective product to consumers.

"We're helping to change that dynamic; we would like to help out both sides. We want to start cutting down on the number of meth labs in communities."

Numbers are hard to quantify, but Leech says rumor has it as many as 80 to 90 percent of the pseudoephedrine products sold over the counter in some areas are diverted into meth production, with pharmacists often tasked with the job of policing their sale.

"While individual pharmacies may monitor their sales, there's not a good system to prevent someone from going to various pharmacies to get these drugs," he adds.

Acura's specialty, says Leech, is in the area of developing pharmaceuticals with a abuse deterrent features, something which began in the area of painkillers prior to the company's work on Nexafed.
On that side of things, the staff at the Culver Acura lab developed a product called Oxecta, used mainly for post-operative pain, but like Nexafed, containing inhibitors to prevent drug abuse.

Leech says there have been challenges generally in getting abuse resistant products into the mainstream. In part, this stems from FDA’s reluctance to allow language on the product's label designating it as an abuse inhibitor, for fear such a label could be read as flawlessly "abuse proof."

One difference between painkillers and Nexafed, says John Gilkay, director of environmental, health and safety, and engineering at the Culver Acura facility, is that painkillers are generally abused "as is," whereas meth is created by chemical alterations to a precursor, in this case, Pseudoephedrine products. This is accomplished in one of a handful of ways. One of the most prevalent is by something often referred to as “shake-and-bake” or “one-pot.” This method results in what is often termed a "meth lab" in the media, but can be little more than a sports drink or soda bottle containing chemicals or residues.
One of Nexafed’s features complicates the generation of liquid solutions needed to make meth.

"It's relatively easy to manufacture a product which would be impossible to get the pseudoephedrine out of if you sacrifice its effectiveness as a decongestant when taken as recommended," Leech explains. "That has really been the trick: having the drug come out so somebody gets the proper therapeutic result, but when somebody tries to convert it to meth, they run into a hurdle."

Leech recognizes that replacing currently-used pseudoephedrine products with Nexafed isn't a cure-all for the meth epidemic, but he and others at Acura believe it could significantly reduce the production of meth, since most of those who actually make meth in rural Indiana and the country as a whole, aren't chemists, but individuals who lack the know-how to work around the inhibitors in Nexafed.

“At some point it comes down to practicality, and finding and executing a reasonable work-around won't be easy.” he notes.
Innocent consumers, meanwhile, have actually been arrested for purchasing too many "precursors," or drugs which could be used to manufacture meth, due to recent laws added to the books. That's a dynamic that Nexafed can also help to change, Leech explains.

"It would be difficult to allege that someone requesting Nexafed is acquiring pseudoephedrine for abuse. I think it will give added confidence to the pharmacist and legitimate consumer at the point of sale."

Gilkay and Leech have been working on Nexafed for the past four years, and in that time, the product has gone through extensive process development, abuse testing and clinical trials to document both the product's efficacy and abuse resistant features. And, they say, the product is priced competitively with other pseudoephedrine products on the market.

Leech emphasizes customers should ask their pharmacist for the product, should they want to see it replace existing Pseudoephedrines.
While Nexafed was fully developed in Culver, its manufacture takes place in Ohio, according to Leech. He points out the ingredients used to inhibit meth production from Nexafed "are safe and commonly used in many pharmaceuticals products.”

Distribution of Nexafed nationally is in "the very early stages," according to Bob Jones. "It doesn't happen overnight. Particularly for a small company, it's our first product we're selling ourselves, and there's a lot of red tape we have to go through, state-by-state, to be eligible in those states...to bring this product into warehouses is a monumental effort."

All involved agree that making a serious shift away from Pseudoephedrine usable in meth manufacture, to a product like Nexafed, will likely require a "grass roots" effort from pharmacists and consumers.

"The pharmacist's number one objective is to treat their consumers the best they possibly can," says Jones. "Like any new product, even though we've done a lot of chemical testing and our product can prove the same efficacy as others, there's always that inkling, 'Does this really work?'"

Leech says he and others at Acura are pressing for smaller, independent pharmacies in the Marshall County and surrounding area to begin carrying it, and the company is advertising the product heavily in several Midwestern and Southern states.

"All of the pharmacists and pharmacies order their drugs from a handful of distributors," Leech points out. "We have Nexafed right now available through Cardinal Health, so (local pharmacists) can order this product now."

Larger chain pharmacies face more of a challenge, and it can be an uphill battle, says Leech.

"I believe that pharmacists and consumers that live in communities affected by meth can quickly see the value in selling a product like Nexafed, but at a corporate level, other business interests may make them less receptive" Gilkay adds.

"It's a great product to watch and work on," says Jones. "(It) can help consumers, communities, and hopefully law enforcement as well. We're awfully proud of what we've done here...(and) the real story is the people in the Culver facility that engineered this technology and proved it will help the meth problem, and the consumer with colds and allergies."

"If we could get our product out there," adds Leech, "we wouldn't be reading about meth every day in the newspaper. We really want to make an impact on communities."

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EXTRA: ACURA HAS MORE THAN 35-YEAR HISTORY IN CULVER

The Acura Pharmaceuticals plant at 16235 State Road 17 in Culver hasn't always been known by that name. Many in the area will recall it as Houba, Inc., a title dating back to at least 1974.

According to John Gilkay, director of environmental, health and safety, and engineering at the Culver Acura facility, the company was started out of a garage attached to the house just south of Acura today, by George Krsek, who had purchased the rights to an antibiotic product called Doxycycline from a company in California.

Under Krsek, a PhD chemist who had worked on a variety of projects, the company expanded.

In the 1990s, Halsey Pharmaceuticals, headquartered in New York, bought the company, says Gilkay.

"In the mid to late `90s, they (Houba) experienced some environmental problems" he explains. "Over the next several years, those issues were resolved and many facility modifications were completed."

Houba was in the process of "negotiating and completing corrective actions when I joined the company in the fall of 2000," Gilkay says. At that time, some of the environmental issues had been worked out while some still needed rectifying.

"When I came here, all of the facility activities revolved around the antibiotic manufacture. It was somewhat unique in that they did the front-end chemical manufacturing of the drug in one part of the facility and then turned that into tablets and capsules in another part of the facility. They also conducted product testing, packaged and shipped Doxycycline products for a variety of customers."

Around 2003, the company had a regime change, with a new CEO who decided to discontinue manufacturing operations at the Culver facility and shut down a New York facility. About 85 percent of the Houba staff in Culver was laid off at that time, says Gilkay, and the focus shifted to creation and development of abuse deterrent products, such as Nexafed.

In conjunction with the change in operational focus, the Culver facility also changed its name from Houba, Inc. to Acura Pharmaceutical Technologies, Inc. Similarly, the publicly traded parent company, Halsey Pharmaceuticals, Inc. became Acura Pharmaceuticals, Inc., still publicly traded despite its small size.

Acura Pharmaceuticals proper has been in business since 2002, says CEO and president Bob Jones, and its corporate headquarters are in Palatine, Illinois, though Jones himself works from New Jersey, while a few in the company work from Atlanta. In all, there are today just 15 members of the Acura company, eight of whom work in Culver.
"So we're very heavily focused towards research and development in how we spend our money," Jones notes.